The Pilot Projects Program (PPP) in the Primary Immune Deficiency Treatment Consortium (PIDTC) will capitalize on the foundation of our main Projects and give opportunities to young investigators to develop new research initiatives. Immediate, near-term and future pilot projects will include: Newborn screening for SCID; Development of a distributed "biobank" of PID samples and data; and Prospective randomized trials of HCT protocols for particular PID subpopulations. For our first pilot project, SCID newborn screening, we will assay for T cell lymphocytopenia by quantitating T-cell receptor excision circles (TRECs) in DMA from dried blood spots. TRECs are present in newly formed T cells, but absent in the blood of infants with SCID, in whom T cell maturation is impaired. Collection and testing of newborn and time-of-diagnosis dried blood spots from PIDTC infants will validate the TREC method for identifying SCID cases. Also, population-based TREC screening will be piloted. A founder mutation in Navajo Indians, resulting in SCID in 1/2000 births, makes this an ideal population for evaluating newborn screening for an otherwise very rare disease. Starting in 2 hospitals and expanding throughout the Navajo Reservation to target of 6000 infants, we will conduct neonatal TREC testing with maternal informed consent. Infants with abnormal screens will receive definitive testing for SCID and referral for early HCT if affected. Valuable cells, DNA and other samples are collected from patients at PIDTC centers, but the rarity of each PID has limited the research possible at any single site. To take advantage of previously collected samples and encourage future research with samples from PIDTC Projects, a multicenter sample bank will be created. Data and samples from all Projects plus findings from further studies conducted on the samples (e.g. SNP genotypes) will accrue so that the value of the sample set will grow over time. Finally, prospective, randomized, multicenter treatment trials will be designed and preformed by PIDTC investigators. Areas of initial focus include monoclonal antibodies to deplete specific lymphoid subsets prior to HCT as an alternative to standard chemotherapy, and special protocols for healthy, but very young infants with SCID, discovered by newborn screening.